Antiviral Combination Formulation With Solid Dispersion for Stable HCV Dosing

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing hepatitis C treatments, such as Compound I and sofosbuvir, face issues with toxicity, side effects, and variability across patient populations, as well as food-effect and drug-drug interactions, limiting their therapeutic effectiveness.

Innovation Solution

A pharmaceutical composition comprising a solid dispersion of Compound I in a polymer matrix with copovidone and about 25% crystalline sofosbuvir, formulated to enhance bioavailability, reduce food-effect, and minimize drug interactions, with a weight ratio of 1:1 for Compound I to copovidone.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Compound I and sofosbuvir are administered alone, then they show antiviral activity, but they exhibit toxicity, side effects, and high variability across patient populations

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtoxicity and side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines Compound I and sofosbuvir into a single pharmaceutical composition with a specific weight ratio (Compound I:sofosbuvir from 1:4 to 4:1). This merging of two antiviral agents into one formulation allows them to work synergistically against HCV while maintaining a favorable safety profile, as evidenced by reduced toxicity and side effects compared to individual administrations.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite pharmaceutical formulation where Compound I and sofosbuvir are combined in specific proportions within a single dosage form. This composite approach leverages the complementary mechanisms of action of both compounds while achieving more consistent therapeutic outcomes across diverse patient populations.

Inventive Principle:

Principle #40Composite materials

2Reliability

If Compound I and sofosbuvir are administered alone, then they treat HCV, but they show food-effect and drug-drug interactions

Engineering Contradiction:

Improvetherapeutic consistencyVSAvoidfood-effect and drug interactions

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

By merging Compound I and sofosbuvir into a single pharmaceutical composition, the patent reduces the number of separate administrations required. This combination approach minimizes food-effect variability and drug-drug interactions that would occur with separate dosing, as the two compounds are delivered together in a controlled ratio within one formulation.

Inventive Principle:

Principle #5Merging (Combining)

3Quantity of substance

If higher doses of Compound I and sofosbuvir are administered, then antiviral coverage is increased, but variability across patient populations increases

Engineering Contradiction:

ImprovedosageVSAvoiddose linearity

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent optimizes the weight ratio parameter of Compound I to sofosbuvir (from 1:4 to 4:1) to achieve improved dose linearity. By carefully controlling this ratio parameter, the formulation maintains consistent pharmacokinetic behavior across higher dose ranges, reducing variability in patient responses while ensuring adequate antiviral coverage.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4005560B1Combination formulation of two antiviral compounds

Publication Date: 2026.02.11 GILEAD PHARMASSET LLC

AI summary

Disclosed are pharmaceutical compositions comprising Compound I, having the formula: and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.